1hne

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[[Image:1hne.gif|left|200px]]<br /><applet load="1hne" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1hne, resolution 1.84&Aring;" />
 
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'''STRUCTURE OF HUMAN NEUTROPHIL ELASTASE IN COMPLEX WITH A PEPTIDE CHLOROMETHYL KETONE INHIBITOR AT 1.84-ANGSTROMS RESOLUTION'''<br />
 
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==Overview==
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==Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-angstroms resolution==
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<StructureSection load='1hne' size='340' side='right'caption='[[1hne]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1hne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HNE FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ALV:(2S)-2-AMINOPROPANE-1,1-DIOL'>ALV</scene>, <scene name='pdbligand=MSU:SUCCINIC+ACID+MONOMETHYL+ESTER'>MSU</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hne OCA], [https://pdbe.org/1hne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hne RCSB], [https://www.ebi.ac.uk/pdbsum/1hne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hne ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[https://omim.org/entry/162800 162800]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[https://omim.org/entry/202700 202700]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hn/1hne_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hne ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.
Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.
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==Disease==
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Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution.,Navia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K Proc Natl Acad Sci U S A. 1989 Jan;86(1):7-11. PMID:2911584<ref>PMID:2911584</ref>
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Known diseases associated with this structure: Hematopoiesis, cyclic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=130130 130130]], Neutropenia, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=130130 130130]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1HNE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Active as [http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HNE OCA].
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</div>
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<div class="pdbe-citations 1hne" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution., Navia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K, Proc Natl Acad Sci U S A. 1989 Jan;86(1):7-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2911584 2911584]
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*[[Elastase 3D structures|Elastase 3D structures]]
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[[Category: Leukocyte elastase]]
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== References ==
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[[Category: Single protein]]
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<references/>
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[[Category: Dorn, C P.]]
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__TOC__
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[[Category: Fluder, E M.]]
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</StructureSection>
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[[Category: Hoogsteen, K.]]
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[[Category: Homo sapiens]]
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[[Category: Lin, T Y.]]
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[[Category: Large Structures]]
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[[Category: Mckeever, B M.]]
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[[Category: Dorn CP]]
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[[Category: Navia, M A.]]
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[[Category: Fluder EM]]
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[[Category: Springer, J P.]]
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[[Category: Hoogsteen K]]
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[[Category: Williams, H R.]]
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[[Category: Lin T-Y]]
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[[Category: hydrolase(serine proteinase)]]
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[[Category: Mckeever BM]]
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[[Category: Navia MA]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:58 2008''
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[[Category: Springer JP]]
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[[Category: Williams HR]]

Current revision

Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-angstroms resolution

PDB ID 1hne

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